This study extends an initial assessment of 765 adolescent offspring (G3s) of the G2 parents enrolled in the New England Family Study (NEFS). The study will capitalize on the unique and extensive individual and family data being collected from both parents and offspring as part of the TTURC-1. The study proposes to conduct follow-up assessments on two occasions to continue to collect individual level data and expands the transdisciplinary (TD) focus of the NEFS study to include information on social contexts. This will provide information at three time points to examine prospectively the mediators and moderators of the effects of neighborhood factors (e.g. SES) on smoking progression and on combined alcohol and other drug use (ATOD). Primary aims include: a). to examine indices of neighborhood disadvantage on smoking progression and ATOD; b). to investigate tobacco access as a mediator of the relationship between neighborhood factor and smoking progression and ATOD; c). to investigate family factors as moderators of the relationship between neighborhood attributes and smoking progression and ATOD. Several exploratory, analyses will also be conducted to examine, for example, individual differences in susceptibility, (e.g., psychopathology) as moderators. This study brings a TD perspective to increase the understanding of the mechanisms underlying the relationships among previously disparate domains of neighborhood, social context, family, and individual differences and the progression of smoking and ATOD. This provides a unique opportunity to expand the experiences of scientists from different backgounds in a TD team effort to better understand interrelationships among contextual, family and individual level. This builds on exciting recent work that suggests that some of the key determinants of smoking progression include community contexts.